In vitro stability and metabolism of salvinorin A in rat plasma.
Xenobiotica; the fate of foreign compounds in biological systems – May 01, 2009
Source: PubMed
Summary
Salvinorin A, a potent natural compound, begins to break down surprisingly quickly in the body. To understand its pharmacology, researchers investigated its stability in plasma. They found that enzymes like carboxylesterase and lactonase are key players in its rapid degradation, converting it into distinct breakdown products such as salvinorin B. This work sheds light on how the body efficiently metabolizes this compound.
Abstract
Salvinorin A is the main active psychoactive ingredient in Salvia divinorum, a Mexican plant that has been widely available as a hallucinogen in recent years. The aims of this study were to investigate the stability of salvinorin A in rat plasma, esterases responsible for its degradation, and estimation of the degradation products. The apparent first-order rate constants of salvinorin A at 37 degrees C, 25 degrees C, and 4 degrees C were 3.8 x 10(-1), 1.1 x 10(-1), and < 6.0 x 10(-3) h(-1), respectively. Salvinorin A degradation was markedly inhibited by the addition of sodium fluoride, an esterase inhibitor. Moreover, phenylmethylsulfonyl fluoride (serine esterase inhibitor) and bis-p-nitrophenylphosphate (carboxylesterase inhibitor) also inhibited salvinorin A degradation. In contrast, little or no suppression of the degradation was seen with 5,5'-dithiobis-2-nitrobenzoic acid (arylesterase inhibitor),ethopropazine (butyrylcholinesterase inhibitor), and BW284c51 (acetylcholineseterase inhibitor). These findings indicated that carboxylesterase was mainly involved in the salvinorin A hydrolysis in rat plasma.4. The degradation products of salvinorin A estimated by liquid chromatography-mass spectrometry included the deacetylated form (salvinorin B) and the lactone-ring-open forms of salvinorin A and salvinorin B. This lactone-ring-opening reactions were involved in calcium-dependent lactonase.